Data from fluid biomarker studies have been critical for defining Alzheimer disease (AD) as a continuum, with pathology developing decades prior to the onset of cognitive symptoms which eventually progress to dementia at the end stage of the disease. This concept is impacting disease nomenclature, diagnostic criteria, prognostic potential, and clinical trial design. Revisions in diagnostic criteria to incorporate biomarker results have recently been proposed in order to increase the confidence of AD as the underlying etiology of a clinical impairment and to permit a diagnosis of AD across the disease continuum, eventually perhaps in the asymptomatic period. Individuals in this ?preclinical? stage are receiving intense focus as a targeted population for secondary prevention trials aimed at identifying disease-modifying therapies that have the best chance of preserving normal cognitive function. The ACS Biomarker Core (Core C) implements well-established and efficient workflows and standard operating procedures for the standardized collection, storage, tracking and sharing of fasted CSF and plasma samples and associated data. Data from samples obtained to date have identified biomarker abnormalities that characterize preclinical AD and have shed preliminary light on the rates of change of these biomarkers in relation to their clinical consequences (i.e., progression from cognitive normality to abnormality). Having already obtained CSF and plasma samples (>600 each) from 337 unique ACS participants (longitudinal samples from 187) who are largely middle-aged, through continued collection of samples (and providing them to Project 2 and other qualified investigators), we will be able to assess whether the biomarker changes initially observed during middle-age are predictive of greater rates of change at older ages and ultimately cognitive decline and progression to dementia. Furthermore, as one of the leading groups in fluid biomarker discovery and world-wide standardization efforts, we will continue to participate in ongoing and future collaborative (and internal) projects involving the performance of current and future biomarker candidates and their assays. Aim 1. Continue to maintain and grow a biorepository of fasted CSF and plasma for present and future studies of aging and AD. Aim 2. Coordinate the distribution of CSF and plasma samples to qualified investigators. Aim 3. Participate in studies regarding fluid biomarker assay development/validation and protocol quality control and standardization efforts.